Functional Imaging of the Human FEF

描述（由申请人提供）：尽管人们普遍认识到前额叶皮层（PFC）对于灵活的行动和有效的感知是必要的，但在理解它实现这些目标的控制机制方面存在根本性的差距。这种知识上的差距是一个关键问题，因为许多精神和神经疾病都源于执行控制的主要功能障碍。长期目标是了解PFC控制运动和感觉系统的机制。当前提案的目的是测试PFC活动如何形成优先空间地图的新模型，该地图标记了视野中显著和相关的位置，然后可以用作执行控制信号的基础。偏见的机制可能涉及到用于扫视计划的机制。该项目的中心目标是测试人类PFC的神经活动模式在多大程度上与优先图理论的预测一致，包括优先图的功能组织、优先级的本质以及优先图读出的效果。这项拟议研究的基本原理是，更好地了解PFC如何发挥控制作用，将导致一个强有力的理论框架，在这个框架内，理解精神疾病的策略将得到发展。目标将是测试，完善，并可能反驳优先图理论的原则，这将通过追求三个具体目标来实现：1)确定额叶皮层中显示优先图标志性特征的候选区域-空间地形组织；2)测试候选优先图的活动是否是各种空间认知使用的基本和一般机制；3)确定优先级图的读出如何影响早期视觉皮层的活动。强有力的初步数据证明了申请人手中项目目标的可行性。在目标1中，使用新颖和优化的地形映射方法确定了PFC中的两个候选优先图。在目标2下，候选优先图中的延迟期活动和大脑活动的多变量模式在各种空间认知任务（例如，记忆，注意力，计划）中即使不能互换，也非常相似。在目标3中，候选优先图的空间特异性持续活动与视网膜匹配的早期视觉区域（即V1， V2, V3）的活动同时存在，这表明候选优先图的活动通过其对早期视觉区域活动的偏倚来指导视觉选择。这种方法是创新的，因为它是高度程序化的；使用新颖的方法来对抗PFC功能神经解剖学中的个体差异；它以创造性的方式使用强大的新分析方法来严格检验关键假设。这项研究具有重要意义，因为它有望测试一种重要的执行控制新模型，并将提供对人类PFC施加控制的机制的详细了解，从而使这些机制的功能障碍模型可以作为神经病理学的原因和潜在治疗的目标。

DESCRIPTION (provided by applicant): Despite the widespread appreciation that the prefrontal cortex (PFC) is necessary for flexible action and efficient perception, there is a fundamental gap in understanding the control mechanisms by which it accomplishes these goals. This gap in knowledge is a critical problem because a host of psychiatric and neurologic disorders stem from a primary dysfunction of executive control. The long-term goal is to understand the mechanisms by which the PFC exerts control over motor and sensory systems. The objective of the current proposal is to test a new model of how activity in the PFC forms maps of prioritized space that tag salient and relevant locations in the visual field, which can then be used as the basis of executive control signals. The mechanisms of bias are likely to involve mechanisms used for saccade planning. The central aim of the project is to test the extent to which the patterns of neural activity in the human PFC are consistent with predictions from the priority map theory, including the functional organization of priority maps, the nature of what is prioritized, and the effects of read-out of priority maps. The rationale for the proposed research is that a better understanding of how the PFC exerts control will lead to a strong theoretical framework within which strategies for the understanding of mental disease will develop. The objective will be to test, refine, and possibly refute, tenets of the priority map theory which will be accomplished by pursuing three specific aims: 1) Identify candidate areas in frontal cortex that show the hallmark feature of priority maps - a spatial topographic organization; 2) Test if activity in candidate priority maps is a fundamental and general mechanism used by a variety of spatial cognitions; and 3) Determine how the read out of priority maps sculpts activity in early visual cortex. Strong preliminary data demonstrate the feasibility of project aims in the applicant's hands. Under aim 1, two candidate priority maps were identified in PFC using novel and optimized topographical mapping approaches. Under aim 2, both delay period activity and multivariate patterns of brain activity in candidate priority maps were remarkably similar, if not interchangeable, across a variety of spatial cognition tasks (e.g., memory, attention, planning). Under aim 3, spatially specific persistent activity in candidate priority maps was concomitant with activity in retinotopically matched early visual areas (i.e., V1, V2, V3) suggesting that activity in candidate priority maps guides visual selection via its biasing of activity in early visual areas. The approach is innovative because it is highly programmatic; uses novel approaches to combat individual differences in the functional neuroanatomy of the PFC; and it uses powerful new analytic methods in creative ways to rigorously test key hypotheses. The proposed research is significant because it is expected to test an important new model of executive control and will provide a detailed understanding of the mechanisms by which the human PFC exerts control, such that models of dysfunction of these mechanisms can be targeted as the causes of and potential treatments for neuropathology. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because advancement in our understanding of the mechanisms by which the prefrontal cortex exerts executive control in the normal brain is necessary to illuminate the mechanisms that could go awry in the pathological brain. Specifically, the proposed research is relevant to NIH's mission because is expected to advance a stronger theoretical framework within which clinical researchers can develop strategies for the diagnosis and treatment of psychiatric and neurologic disorders.